Oncology phase II clinical trials are used to evaluate the initial effect of a new regimen to determine if there warrants further study in a phase III clinical trial. Two-stage designs with an early futility stop are commonly used in these phase II trials. It is common for attained sample sizes in these trials to be different from the designed sample sizes due to over- and under- enrollment. Currently, when the attained sample size differs from that planned, common practice is to treat the attained sample sizes as planned, and this practice leads to invalid inference. In this thesis, we examine the problems and solutions in hypothesis testing for two-stage phase II clinical trial designs when attained sample sizes differ from the planned sample sizes. We describe existing methods for redesigning trials when there is over- or under-enrollment in either the first or second stage and introduce a new method for redesigning a two-stage clinical trial when the first stage sample size deviates from planned. We focus our investigation when there is over- or under-enrollment in the first stage. We compare the frequentist methods of Chang et al., Olson and Koyama, and the Likelihood two-stage design by applying these methods to two-stage designs with deviations in the first stage of +/- 10. We examine type I error rates, power, probability of early termination and expected sample size under the null hypothesis in a number of two-stage designs. We also compare error rates in these methods using a Monte Carlo simulation.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-06132017-150729 |
| Date | 20 June 2017 |
| Creators | Olson, Molly Ann |
| Contributors | Tatsuki Koyama, Jeffrey Blume |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-06132017-150729/ |
| Rights | restrictsix, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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